A 62-year-old man with a complaint of back pain lasting 2 months was admitted. He also presented a huge abdominal tumor. Diagnostic imaging showed metastatic tumors in the liver, lumbar vertebrae and bilateral lung. An ultrasound-guided needle biopsy revealed a lung tumor containing melanic tissue. Subsequently, there was an evident elevation in uric acid, phosphoric acid, potassium and lactate dehydrogenase concentrations in serum. Continuous hemodiafiltration and administration of rasburicase was initiated following the diagnosis of tumor lysis syndrome (TLS). However, he died on the fourth day owing to arrhythmia. An autopsy revealed metastatic deposits in the liver, lung, spine, ribs, and lymph nodes along the biliary system. Microscopic examinations revealed massive necrosis of normal hepatocytes and tumor cells with disseminated tumor thrombi in the portal system. The catastrophic progression of TLS appears to be influenced by a persistent portal blood flow deficiency by portal tumor thrombus in this case.